The ability to grow mammalian cells at the laboratory, clinical and industrial levels is often important. Some mammalian cell types have been adapted for growth in suspension cultures, but other mammalian cell types will grow only if they can become attached to an appropriate surface. The latter cell types are generally termed "anchorage-dependent". Anchorage-dependent cell types include such important cell lines as 3T3 mouse fibroblasts, mouse bone marrow epithelial cells; Murine leukemia virus-producing strains of mouse fibroblasts, primary and secondary chick fibroblasts; WI-38 human fibroblast cells; and normal human embryo lung fibroblast cells.
Anchorage-dependent cells are typically grown in culture vessels such as dishes and flasks. More recently, larger scale propagation of anchorage-dependent mammalian cells has been achieved in roller tubes and roller bottles. In such instances, the anchorage-dependent cells attach to the glass surface of the bottle or to the polymeric material forming the bottom of a culture dish or flask. Nevertheless, it has been found that many common polymeric materials, e.g., polymethyl methacrylate, are unsuitable for cell attachment and growth.
On the other hand, collagen, a natural protein derived from animal sources has long been known to be a substrate capable of promoting cell adhesion and growth. Other proteins are also known to support growth of at least certain cell lines, and it is also known that other macromolecules can support cell growth.
One class of synthetic polymeric materials which have found wide application as biomaterials is the class known as hydrogels. The term "hydrogel" refers to a broad class of polymeric materials which are swollen extensively in water but which do not dissolve in water. Generally, hydrogels are formed by polymerizing a hydrophilic monomer in an aqueous solution under conditions where the polymer becomes crosslinked so that a three-dimensional polymer network sufficient to gel the solution is formed. Hydrogels are described in more detail in Hoffman, A. S., "Polymers in Medicine and Surgery," Plenum Press, New York, pp 33-44 (1974).
Hydrogels have many desirable properties for biomedical applications. For example, they can be made nontoxic and compatible with tissue, and they are usually highly permeable to water, ions and small molecules. Despite these favorable properties, hydrogels have been found, in general, to be unsuitable as substrates for cell attachment and growth. In fact, a hydrogel based upon polyhydroxyethyl methacrylate was employed in one study as a coating on standard tissue culture flasks to prevent fibroblast growth. Folkman, J. and Moscona, A., Nature, 273, 345-9 (1978).